Introduction
The World Health Organization reports cardiovascular disease to be a leading cause of death in humans worldwide,1 and cardiovascular diseases also affect animals. Although various phenotypes fall under the cardiovascular disease umbrella, alteration in arterial blood pressure (BP) can be a sequela or an inciting cause. The American Heart Association recommends measurement of arterial BP every 3 to 6 months in human patients with cardiovascular disease, depending on severity,2 and the American College of Veterinary Internal Medicine (ACVIM) consensus statement on hypertension has similar recommendations for veterinary patients.3
Chimpanzees (Pan troglodytes) are a common species in zoological institutions and often serve in research models for various human diseases. Unfortunately, chimpanzees have a propensity to develop cardiovascular disease in captive settings.4 A recent review5 of spontaneous causes of death in a large chimpanzee colony over 35 years reported cardiovascular disease as the most common cause. Although cardiomyopathies appear to be the predominant pathology, arteriosclerosis or atherosclerosis seems to be a coexisting factor, particularly in female chimpanzees.6 Despite a recent report7 suggesting that the mechanism for heart disease in humans and chimpanzees may differ,7 BP measurement is typically performed as part of the diagnosis and monitoring of cardiovascular disease in both species.8,9 In addition, measuring BP is recommended when feasible for any patient undergoing anesthesia or immobilization, because of the potential for substantial derangements in cardiovascular homeostasis.10
Direct BP measurement through the use of arterial catheterization is the gold standard for the evaluation of arterial BP; however, this technique is invasive and technically challenging and requires specific, expensive monitoring equipment.11 Noninvasive techniques for measuring arterial BP, such as oscillometry, are typically used in chimpanzees in clinical settings,8,12 and reference intervals for arterial BP measurements by oscillometry in chimpanzees have been published recently.13 Although oscillometry provides results that have reasonable agreement with direct BP measurements in humans,14 dogs,15 and other companion animals,16–18 to our knowledge, agreement between direct and indirect BP measurements has not been evaluated in chimpanzees. To use oscillometry to measure BP and apply oscillometric reference intervals for the diagnosis of hyper- or hypotension in chimpanzees, the accuracy of the technique needs to be verified in the species. Therefore, a comparison between direct BP measurement (gold standard) and oscillometric BP measurement (alternative measurement technique) needs to be performed to assess agreement and determine bias (the mean difference between the 2 techniques) and 95% limits of agreement (LOA; ± 1.96 SD of the mean difference) of oscillometry in chimpanzees.19
The primary objective of the study reported here was to evaluate the level of agreement between direct and oscillometric BP measurements in anesthetized chimpanzees. Our secondary objectives were to determine the ability of oscillometry with brachial or digit cuffs to detect hypotension and to evaluate whether either technique would meet the ACVIM criteria for accurate BP measurement. We hypothesized that results for oscillometry would reasonably agree with direct BP measurements for normotensive animals; that as direct BP measurements deviate from the reference limits, accuracy of oscillometry would decline; and that the brachial cuff would perform better than the digit cuff.
Materials and Methods
Animals
The evaluation of direct versus indirect BP measurement was 1 portion of a multipart study20 that was approved by The University of Tennessee’s Institutional Animal Care and Use Committee (No. 2643-0918) and conducted between March 2018 and January 2019. Eight healthy adult captive chimpanzees (5 females and 3 males) housed at Chattanooga Zoo and Zoo Knoxville in Tennessee and scheduled to undergo anesthesia for their annual routine examinations were eligible for the study. The health status of each animal was based on results of physical examination, biochemical analyses, a CBC, and echocardiography. Animals were excluded if they were determined to have been unhealthy or an arterial catheter could not have been placed.
Study design
On the basis of previously obtained results for body weight, all animals were anesthetized with a combination of dexmedetomidine (0.02 mg/kg), ketamine (5 mg/kg), and midazolam (0.06 mg/kg) administered IM by manual injection or remote dart injection. After confirmation of immobilization, each animal was positioned in dorsal recumbency, orotracheally intubated, and equipped for monitoring (V Monitor; VetTRENDS System Medical Inc) of ECG, pulse oximetry end-tidal partial pressure of carbon dioxide and isoflurane concentration, rectal temperature, and oscillometric BP. The same multiparameter monitor (V Monitor; VetTRENDS System Medical Inc) was used for all animals. Each animal received oxygen (2 L/min) delivered through a circle breathing system connected to an anesthesia machine and was allowed to spontaneously breathe. If the end-tidal partial pressure of carbon dioxide exceeded 50 mm Hg, intermittent positive-pressure ventilation was performed. Isoflurane in oxygen was delivered through this system as needed for additional anesthesia.
Two brachial cuffs (either a No. 10 or No. 11; FlexiPort Reusable Blood Pressure Cuffs; Welch Allyn Inc) were used, with selection and placement always to approximate 40% limb circumference of animals of different sizes and always on the left brachium over the brachial artery. In addition, a digit cuff (1 cuff adequately fit all animals) was placed on the second digit of the contralateral forelimb. The digit cuff was approximately 40% of the circumference of the digit and was attached to a different monitor (PetMAP; Ramsey Medical Inc). For direct BP measurement, a 20-gauge, 1.5-inch catheter (Surflo; Terumo Medical Corp) was aseptically placed in either the right or left tibial artery (Figure 1). The catheter was then connected to noncompliant tubing filled with heparinized saline (0.9% NaCl) solution and connected to a BP transducer (Deltran; Utah Medical Products Inc). The transducer was new for each animal and connected to both the multiparameter monitor and a pressurized (> 300 mm Hg) bag of heparinized saline solution. With the animal in dorsal recumbency, echocardiography was used to identify the animal’s right atrium, the level of which was then used as the zero-reference point for the BP transducer. After the transducer was positioned appropriately, the BP measuring system was zeroed to atmospheric pressure, and a dynamic pressure response test was performed to confirm the system was not over- or underdamped. It was ensured that the positions of the brachium and digit around which the cuffs had been placed were at the same level as the right atrium and BP transducer for all measurements. Direct BP measurements were recorded at the same time that oscillometric data were generated by the monitor for each cuff, and these were considered paired measurements (direct versus oscillometric brachial cuff measurements of BP and direct vs oscillometric digit cuff measurements of BP). Because of the relatively short time allowed for data collection, replicate measurements were not performed; thus, all paired readings indicated 1 measurement time point. All data were recorded by the same observer every 5 minutes during general anesthesia.

Representative photograph of 1 of the 8 captive adult chimpanzees (Pan troglodytes) undergoing general anesthesia for a regularly scheduled annual physical examination between March 2018 and January 2019, showing the medial aspect of the right pelvic limb with an arterial catheter placed in the tibial artery for direct measurement of blood pressure (BP). The chimpanzee is in dorsal recumbency, and its head is toward the top of the image.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194

Representative photograph of 1 of the 8 captive adult chimpanzees (Pan troglodytes) undergoing general anesthesia for a regularly scheduled annual physical examination between March 2018 and January 2019, showing the medial aspect of the right pelvic limb with an arterial catheter placed in the tibial artery for direct measurement of blood pressure (BP). The chimpanzee is in dorsal recumbency, and its head is toward the top of the image.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
Representative photograph of 1 of the 8 captive adult chimpanzees (Pan troglodytes) undergoing general anesthesia for a regularly scheduled annual physical examination between March 2018 and January 2019, showing the medial aspect of the right pelvic limb with an arterial catheter placed in the tibial artery for direct measurement of blood pressure (BP). The chimpanzee is in dorsal recumbency, and its head is toward the top of the image.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
As part of the concurrent study,20 echocardiography was being performed simultaneously as we collected BP data. That concurrent study was conducted in 2 phases. Phase 1 began with the first contact with the animal, included the first of 2 echocardiographic examinations, and concluded with the administration of the atipamezole (0.2 mg/kg, IM) to reverse the effects of dexmedetomidine. Isoflurane in oxygen was then administered to maintain an adequate plane of anesthesia, and an interim period of 15 minutes was allotted before phase 2 began with the onset of the second echocardiographic examination. Phase 2 ended when the second echocardiographic examination concluded. Isoflurane was then discontinued, the arterial catheter for direct BP measurement was removed, and the chimpanzee was moved to a recovery area for observation. After a recovering chimpanzee swallowed or coughed, the animal was extubated, and then the remaining monitoring devices were removed. The chimpanzee was left in an enclosure and monitored visually until its righting reflex returned.
Statistical analysis
Agreement between direct and oscillometric measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) was assessed for each oscillometric cuff site (brachial and second digit of the contralateral forelimb) with the use of Bland-Altman plots for multiple observations per individual.19 The difference between results for direct versus oscillometric BP measurements was the bias, and a positive or negative bias indicated that the oscillometric measurement over- or underestimated the direct measurement, respectively. The mean bias and 95% LOA were calculated (MedCalc version 19.0.7; MedCalc Software Ltd), with the 95% upper and lower LOA as 1.96 SD above and below the mean bias, respectively. Regression analysis (R version 3.6.1; The R Foundation) was performed to test whether the bias for oscillometry at each cuff site was consistent over the range of measurements, and Bland-Altman plots with regression lines were generated (R ggplot2 package version 3.2.0; Wickham H, Chang W, Henry L, et al). Given that for SAP and DAP the ACVIM recommends that ≥ 50% of measurements obtained with a test method be within ± 10 mm Hg of measurements obtained with the gold standard method and that ≥ 80% of measurements obtained with a test method be within ± 20 mm Hg of measurements obtained with the gold standard method,19 the percentages of oscillometric measurements at each cuff site that were within ± 10 or 20 mm Hg of the paired direct BP measurement were also calculated.
Hypotension was defined as a direct measurement of SAP < 80 mm Hg or of MAP < 60 mm Hg. Sensitivity for detecting hypotension was calculated for each oscillometric cuff site (brachium or second digit of the contralateral forelimb) as the number of oscillometric BP measurements that correctly indicated hypotension divided by the number of direct BP measurements that indicated hypotension. Specificity for oscillometry at each cuff site was calculated as the number of oscillometric measurements that correctly indicated normotension divided by the number of direct measurements that indicated normotension.
Results
All 8 chimpanzees were deemed healthy on the basis of results of physical and clinicopathologic examinations, and all 8 chimpanzees successfully completed the study. Body weight ranged from 48 to 75 kg, with a mean body weight of 61.7 kg for females (n = 5) and 65.9 kg for males (3).
All chimpanzees were immobilized with the anesthetic agents administered IM; however, 4 chimpanzees also required isoflurane delivered in oxygen by mask to allow placement of the endotracheal tube. Isoflurane in oxygen was also administered to maintain anesthesia in all animals after atipamezole was administered at the end of phase 1 of the concurrent study.20 Mean ± SD duration of anesthesia was 44 ± 6 minutes. Hypotension was the only observed anesthetic complication and was observed in all 8 animals and 37 of the 74 (50%) direct MAP measurements. The duration of observed hypotension was typically between 15 and 25 minutes, and results for end-tidal partial pressure of carbon dioxide, end-tidal isoflurane concentrations, pulse oximetry, ECG, and rectal temperature remained within acceptable limits. All chimpanzees recovered from anesthesia without issue, and at last follow-up, approximately 2 years after the anesthetic events, none of the 8 animals that had hypotension during anesthesia had any detectable consequences later attributed to their period of hypotension.
Overall, there were 74 paired direct and brachial oscillometric measurements of each, SAP, MAP, and DAP and 66 paired direct and digit oscillometric measurements of each, SAP, MAP, and MAP. Bland-Altman plots were generated to compare results for direct versus oscillometric BP measurements. Brachial oscillometry of MAP had the least mean bias (0.8 mm Hg; 95% LOA, –29 to 31 mm Hg; Figure 2; Table 1), whereas oscillometric measurements of SAP obtained from the second digit of the contralateral forelimb had the greatest mean bias (7.8 mm Hg; 95% LOA, –40 to 55 mm Hg; Figure 3).



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a brachial cuff to determine systolic arterial pressure (SAP; A), mean arterial pressure (MAP; B), and diastolic arterial pressure (DAP; C) in the 8 anesthetized chimpanzees described in Figure 1. The top and bottom dashed horizontal lines represent the upper and lower limits of the 95% limits of agreement (1.96 SD above and below the mean difference, respectively), the middle dashed line is the mean bias (mean difference between direct and oscillometric measurements), the solid bold line represents the regression line, and each square represents a set of paired direct and oscillometric (brachial) BP measurements (n = 74). OBP = Oscillometric BP.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
The American College of Veterinary Internal Medicine (ACVIM) criteria for validation of oscillometric methods and results for variables of interest for paired oscillometric and direct measurements of blood pressure (BP) in 8 anesthetized captive chimpanzees (Pan troglodytes) between March 2018 and January 2019, stratified by oscillometric cuff site (brachial [n = 74] or contralateral forelimb second digit [66]) and BP type (systolic arterial pressure [SAP], mean arterial pressure [MAP], or diastolic arterial pressure [DAP]).
Variable | Mean bias (mm Hg) | SD (mm Hg) | 95% LOA (mm Hg) | Percentage (proportion) within ± 10 mm Hg* | Percentage (proportion) within ± 20 mm Hg* | Sensitivity for hypotension (%) | Specificity for hypotension (%) | No. (%) of hypotensive direct BP measurements |
---|---|---|---|---|---|---|---|---|
ACVIM criteria | Within ± 10 | Within ± 15 | ± 30 | ≥ 50 | ≥ 80 | — | — | — |
Brachial OBP | ||||||||
SAP | 4.6† | 26.7 | –48 to 57 | 34 (25/74) | 55 (41/74) | 54 | 100 | 28 (38) |
MAP | 0.8† | 15.2 | –29 to 31 | 49 (36/74) | 87 (64/74)† | 78 | 95 | 37 (50) |
DAP | –3.1† | 15.8 | –34 to 28 | 60 (44/74)† | 81 (60/74)† | — | — | — |
Digit OBP | ||||||||
SAP | 7.8† | 24.2 | –40 to 55 | 41 (27/66) | 67 (44/66) | 50 | 93 | 24 (36) |
MAP | 1.2† | 17.4 | –33 to 35 | 49 (32/66) | 74 (49/66) | 66 | 94 | 32 (49) |
DAP | –5.1† | 18.9 | –42 to 32 | 58 (38/66)† | 77 (51/66) | — | — | — |
Indicates the percentage and proportion of oscillometric measurements within ± 10 or ± 20 mm Hg of the paired direct BP measurement, as specified by the ACVIM criteria. †Value is in agreement with the ACVIM criteria.
— = Not applicable. LOA = Limits of agreement.



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194



Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
Bland-Altman plots for analyses of agreement between results for direct BP measurement (gold standard) obtained with the use of tibial artery catheterization and oscillometric BP measurement obtained with the use of a cuff placed around the second digit of a forelimb to determine SAP (A), MAP (B), and DAP (C) in the anesthetized chimpanzees described in Figure 1. Each square represents a set of paired direct and oscillometric (digit cuff) BP measurements (n = 66). See Figure 2 for the remainder of the key.
Citation: American Journal of Veterinary Research 82, 12; 10.2460/ajvr.20.11.0194
The sensitivity and specificity for oscillometry to detect hypotension on the basis of SAP and MAP were evaluated (Table 1). Only brachial oscillometric measurements of MAP had adequate sensitivity (78%) and specificity (95%) to accurately detect hypotension, whereas the sensitivity was insufficient for detecting SAP hypotension by oscillometry with a brachial cuff (54%) or digit cuff (50%) or MAP hypotension with a digit cuff (66%). Additionally, the ACVIM criteria for a test method to have ≥ 50% and ≥ 80% results within ± 10 and ± 20 mm Hg, respectively, of the gold standard results for SAP and DAP were applied to all results in the present study. Brachial oscillometry yielded 49% (36/74) and 87% (64/74) of MAP measurements within ± 10 or ± 20 mm Hg, respectively, of the paired direct measurements and 60% (44/74) and 81% (60/74) of DAP measurements within ± 10 or ± 20 mm Hg, respectively, of the paired direct measurements.
Discussion
To our knowledge, the present study was the first to report the overall agreement between direct and oscillometric BP measurements in chimpanzees. Our findings indicated that MAP measured with brachial oscillometry reasonably agreed with results obtained with direct BP measurement and could be used reliably to diagnose hypotension in the chimpanzees of the present study.
A recent study12 of BP in healthy adult chimpanzees established oscillometric BP reference intervals but did not compare results for oscillometry versus direct pressure measurement (the gold standard) to evaluate whether oscillometry was an adequate surrogate for direct BP measurement. For such oscillometric measurements to be used with confidence, the technique first would need to be evaluated for accuracy in the species.
The Association for the Advancement of Medical Instrumentation, which evaluates and validates human medical instruments, requires the mean difference (bias) between the gold standard and the proposed alternative techniques to be ≤ 5 mm Hg and the SD to be ≤ 8 mm Hg.20 Because of these strict limits combined with the difficulty in obtaining noninvasive BP measurements in animals, the ACVIM guidelines suggest a mean difference (bias) of ≤ 10 mm Hg and a SD of ≤ 15 mm Hg for SAP and DAP measurements to be considered accurate.19 With the ACVIM suggested limits and given a 95% LOA, basically 2 SDs above and below the mean bias, the recommended LOA would be ± 30 mm Hg. A wider LOA would cause concern about inaccuracy. In the present study, the mean bias when measuring SAP, MAP, and DAP was < 5 mm Hg for oscillometric measurements with a brachial cuff and < 10 mm Hg for those measured with the digit cuff. These findings indicated that the mean bias for each was within the limits suggested in the ACVIM guidelines. However, only the results for MAP measured with the brachial cuff also met the ACVIM criteria for SD. Additionally, when considering the percentage of oscillometric BP measurements for each cuff site that were within ± 10 or ± 20 mm Hg of the paired direct BP measurements, brachial oscillometry performed well with 49% (36/74) and 87% (64/74), respectively, of MAP measurements and 60% (44/74) and 81% (60/74), respectively, of DAP measurements but did not perform well for SAP measurements (34% [25/74] and 55% [41/74], respectively). Our findings that brachial oscillometry performed well when measuring MAP and DAP but not SAP were similar to findings of studies21,22 that evaluated agreement between direct and indirect BP measurement techniques in dogs. This could relate to findings in human medicine that there is agreement in aortic and radial artery MAP and DAP, whereas peripheral SAP often increases as the distance from the aorta increases, which is a phenomenon seemingly caused by arterial resonance properties.23 Moreover, the algorithm used by a given monitor may influence findings, because some oscillometric monitors measure SAP and DAP and calculate MAP whereas others measure MAP and determine SAP and DAP algorithmically. In the present study, ACVIM criteria for accurate BP measurement were only met by brachial oscillometry of MAP, whereas the ACVIM criteria were not met with digit oscillometry for SAP, MAP, or DAP. These findings supported our hypothesis that a brachial cuff would perform better than a digit cuff.
Ideally, a Bland-Altman plot of a gold standard technique plotted against a tested technique would reveal a horizontal line parallel with the bias and devoid of a positive or negative regression line, indicating that the investigated technique has accuracy across a wide range of possibilities. The negative regression seen in all 6 Bland-Altman plots in the present study indicated that the oscillometric techniques used did not consistently and accurately predict BP when direct BP measurements indicated hypo- or hypertension. The general pattern seen in all plots suggested that oscillometry, as performed in the present study, overestimated BP when it was low (positive bias) and underestimated BP when it was high (negative bias). The positive bias of such oscillometric techniques during hypotension would be problematic for accurate diagnosis and management of hypotension and has been reported in other species, including humans.14,24,25 Similarly, and consistent with studies11,22,25,26 in dogs, our finding of a negative bias during high BP would complicate the diagnosis of hypertension. These findings confirmed our hypothesis that as direct BP measurements deviate from the reference limits, the accuracy of oscillometry with a brachial or digit cuff would decline.
Hypotension is a common complication for anesthetized patients across species and increases anesthesia-related morbidity and death. For this reason, accurate measurement of BP in anesthetized patients is paramount for clinicians’ abilities to diagnose hypotension, implement appropriate interventional treatments, and improve successful outcomes. Our results indicated that only brachial oscillometric measurements of MAP had adequate sensitivity (78%) and specificity (95%) to accurately detect hypotension. In contrast, the sensitivities of brachial and digit cuffs in measuring SAP (54% and 50%, respectively) and of a digit cuff in measuring MAP (66%) were too low to accurately detect hypotension.
The present study had limitations. The sample size of 8 chimpanzees was small in terms of applying our results to a general population; however, the number of eligible animals was predetermined by a preexisting schedule for annual examinations of chimpanzees at the participating facilities. However, results of a post hoc power analysis indicated that the 74 paired brachial oscillometric and direct BP measurements had a power of 0.87 to evaluate agreement with a confidence level for the LOA of 0.95, maximum allowable difference of 40 mm Hg, and mean ± SD of differences of 0.43 ± < 15 mm Hg. Thus, the agreement evaluation between brachial oscillometric and direct BP measurements had adequate power.
Another limitation was that the results could have been specific to the monitors, their respective algorithms, and the positions of the cuffs and arterial cannulae in the present study. The Great Ape Heart Project did not recommend a particular device for measuring BP in chimpanzees; thus, we used 1 monitor for brachial oscillometric measurements and a different monitor for oscillometric measurements obtained from the cuff placed on the second digit of the contralateral forelimb. Both monitors had been used clinically before the present study. Furthermore, findings from a study27 in horses suggest that the anatomic location of oscillometry cuff placement can alter agreement with direct BP measurement and that different sites of arterial catheterization can yield differences in measurements.
Additionally, the anesthetic protocol may have affected the performance of the oscillometric monitors. For instance, vasoactive medications (eg, dexmedetomidine used in the present study) affect the accuracy of these monitors.26 However, the immobilization protocol in the present study was aligned with common clinical practice and thus represented conditions veterinarians would likely encounter during chimpanzee immobilization. Lastly, results of a validation test are only applicable to the species and conditions in which they were tested.19 Thus, our results may only be applied to anesthetized chimpanzees. Future research with a larger sample size of chimpanzees could evaluate direct versus oscillometric BP measurements when BP is manipulated to generate hypo-, normo-, and hypertensive conditions. Another potential investigation could be to evaluate different sizes of cuffs and anatomic locations of cuff placement to determine whether a cuff width of 30% to 40% of the appendage site circumference is appropriate for chimpanzees, given that this size range is inaccurate in horses.27 Additionally, further research is needed to investigate variables affecting accurate BP measurement with noninvasive techniques and the applicability of indirectly measuring BP in awake chimpanzees.
Acknowledgments
No external funding was used in this study. The authors declare that there were no conflicts of interest.
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